The goal of this proposal is to develop a new topical formulation for the treatment of intermittent claudication. Intermittent claudication is the primary symptom of peripheral arterial disease, and it affects over 4 million individuals in the United States. Given orally, L-carnitine has shown great promise in clinical trials, however, its bloavailability is poor. Current treatments involve high doses over a prolonged period of time. A more efficient and faster treatment could be provided when the drug is applied topically, thus allowing direct transport into the underlying muscle tissue. To enhance transdermal delivery, L-carnitine will be formulated in a liposomal delivery system, which has already been proven to be successful for the topical delivery of other drugs. First, the carbon chain length of alkyl-L-carnitine will be optimized with respect to encapsulation efficiency and physico-chemical stability of the formulation. Second, the formulation will be optimized with respect to L-carnitine transport through skin in vitro. Finally, in vivo proof of concept will be obtained of L-carnitine delivery into muscle tissue. The best formulation will be identified and developed for further clinical testing. PROPOSED COMMERCIAL APPLICATION: Currently, there is no topical drug treatment for intermittent claudication (IC). Last year a new oral drug (Pletal) was launched. This was the first drug for the treatment of intermittent claudication to reach the market in 15 years. Despite its poor bioavailability and questionable efficacy, this drug grossed 90 million US dollars. This is a striking example of the clinical need for such a drug. A topical formulation should provide a fast and efficient relief from this debilitating disease.